1. Field of the Invention
The present invention relates generally to pre-filled plastic syringes and containers containing liquid pharmaceutical, biological or veterinary products therein and to a process for terminal sterilization thereof. More particularly, the invention relates to pre-filled plastic syringes containing liquid contrast media for parenteral administration and to a process for terminal sterilization thereof.
2. Reported Developments
The prior art discloses processes, apparatus and containers for the sterilization of products and medical devices used in the health and medical fields where sterilization is an absolute requirement. Generally speaking, such sterilization may be accomplished by sterilizing the containers and contents separately, followed by placing the contents into the containers and hermetically sealing the same for use at a later time. However, such processes carry the risk of contamination and introduction of pyrogens during transfer of the products into their containers. The preferred method of achieving sterile finished products or ready to use sterile medical devices is through the use of terminal sterilization by autoclaving.
In the process of terminal sterilization, the pre-filled containers/packages are placed in an autoclave and are subjected to operational cycles which include: creating a vacuum in the autoclave by evacuating air therefrom; introducing steam in the autoclave so that the temperature therein reaches about 270.degree. F.; maintaining the temperature for a time sufficient to sterilize the content of the autoclave; vacuum drying for about one hour while maintaining the temperature around 270.degree. F.; and cooling the autoclave and removing the containers therefrom. Typical containers containing parenteral formulations, such as glass ampules, stoppered vials and bottles are able to withstand the pressure differentials between the containers and the autoclave chamber created by the operational cycles of the sterilization process. However, pre-filled syringes and cartridges made of plastic do not tolerate significant pressure differentials when the internal pressure is greater than the external; such pressure differential results in deformation and warping of the plastic walls that will occur either during the heating phase or the cooling phase of the autoclave cycle.
As a consequence, provision must be made to prevent deformation of container walls which may cause leakage of content through separation of seal of the container and contamination of the product from the environment during the process of terminal sterilization and subsequent shelf-life. The problem associated with pressure differential has been overcome by a method disclosed in U.S. Pat. No. 4,718,463, which provides for maintaining a pressure on the outside surfaces of the syringe at least equal to the pressure inside the syringe during autoclaving, i.e. by maintaining an autoclave overpressure.
The present invention provides a method for terminal steam sterilization of pre-filled plastic containers and syringes without the necessity of autoclave overpressure.
The present invention also provides pre-filled plastic containers and syringes that are steam sterilizable essentially without risk of deformation, leakage of content and contamination.
Other objects, features and advantages of the present invention will be apparent from the description that follows.